Non-Classic Myeloproliferative Neoplasms: Are We Really Aware of These Rare Diseases in Daily Practice?

Abstract

Chronic neutrophilic leukaemia (CNL), chronic eosinophilic leukaemia-not otherwise specified (CEL-NOS), and myeloproliferative neoplasm (MPN), unclassifiable are rare clonal diseases, known as ‘non-classic myeloproliferative neoplasms’. They are diagnosed largely based on exclusion of underlying reactive causes by patient history, physical examination, serological tests, and imaging studies. As well as peripheral blood testing, bone marrow examination is mandatory to exclude bone marrow infiltrating conditions such as multiple myeloma, acute leukaemias, etc. Today, molecular genetic classification should be undertaken to establish accurate diagnosis, in addition to the traditional morphological classification of MPN. Therefore, molecular genetic testing should take part in the diagnostic work-up of suspected patients with rare MPN. Of CNL patients, 90% (and in some datasets 100%) have mutations in CSF3R, which has led to the addition of this finding to the diagnostic criteria for CNL. The absence of rearrangements of FIP1L1/PDGFRA, PDGFRA, PDGFRB, FGFR1, and PCM1-JAK2 fusions should prompt consideration of a diagnosis of chronic eosinophilic leukaemia-not otherwise specified. MPN, unclassifiable, the least frequent type, is considered when an MPN has definite MPN features but does not meet diagnostic criteria for either the classic or the other non-classic MPN. They all share common symptoms and findings. Transformation to acute leukaemia is still a major clinical problem. Since no standard of care exists, the treatment approach is still symptomatic for all. This is an indicator that we really need disease-modifying drugs against initial diagnostic molecular markers, such as CSF3R inhibitors, which might change the natural history of these disorders. Therefore, participation in clinical trials is mandatory for this extremely rare patient population.